High cholesterol primary prevention

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Template:Hypercholesterolemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Associate Editor(s)-In-Chief: Kashish Goel, M.D.

Overview

Primary prevention is the most effective means of reducing the global burden of cardiovascular disease. NCEP recommends population-based and clinical-based approaches for primary prevention. Physicians should establish short-term and long-term goals for their patients based on risk factors and 10-year CHD risk. Two-step approach is preferred:

Therapeutic lifestyle changes

Therapeutic lifestyle changes should be recommended to every individual to reduce long-term risk. These include cessation of smoking, dietary modifications, weight control and physical inactivity. A previous meta-analysis showed that dietary lowering of cholesterol was associated with CHD risk reduction similar to drug therapy[1]. A recent randomized controlled trial by Jenkins et al. showed that cholesterol lowering diets were associated with a significant reduction in LDL and 10-year CHD risk at 6 monhts, as compared to control diet[2].


LDL lowering drug therapy

LDL lowering therapy for primary prevention has been evaluated in numerous trials. If therapeutic lifestyle changes do not achieve the desired LDL goal, then drug therapy should be considered. Statins are usually the 'first choice' medications. Trials evaluating the role of statin therapy in primary prevention are detailed here.

Meta-analysis

  • A recently published Cochrane meta-analysis including 14 randomized controlled trials (34,272 participants) showed a significant reduction in all-cause mortality, combined fatal and non-fatal CVD endpoints and revascularizations with statin therapy in subjects without cardiovascular disease. However, they reported heterogeneity of effects between studies[3].
  • Another meta-analysis evaluating the role of statins in primary prevention of cardiovascular disease showed a significant reduction in major coronary events, major cerebrovascular events and revascularizations in 42, 848 participants, however no change in coronary heart disease mortality or overall mortality was noted[4].

Randomized controlled trials

  • WOSCOPS (1995): Treatment with pravastatin 40 mg daily in 6595 men with hypercholesterolemia resulted in a significant reduction in the incidence of fatal and non-fatal myocardial infarction and death from cardiovascular causes, without a difference in the deaths due to non-cardiovascular causes in a follow-up period of 4.9 years[5].
  • AFCAPS/TexCAPS (1998): Lovastatin 20-40 mg daily (in addition to low-saturated ad low-colesterol diet) reduced the incidence of first major acute cardiovascular event (MACE) during a follow-up of 5.2 years, in this study involving 5608 men and 997 women with average total cholesterol and LDL levels and low HDL levels[6].
  • PROSPER (2002): Pravastatin 40 mg daily reduced the incidence of non-fatal MI and CHD death during a follow-up of 3.2 years, in this trial involving the 2804 elderly men and 3000 women with a history of, or risk factors for vascular disease. This trial extended the treatment strategies to elderly population and showed that treatment with statins may also have a role in prevention of transient ischemic attacks[7].
  • ALLHAT-LLT (2002): No significant difference was observed on CHD mortality in the group treated with pravastatin 40 mg daily as compared to the usual care group with well controlled hypertension and moderately elevated LDL. Possible explanations for failure to observe a significant reduction included a modest reduction in total cholesterol, unblinded study with no placebo group and a large crossover of high risk subjects[8]
  • ASCOT-LLA (2003): Hypertensive patients with total cholesterol < 251 mg/dL were randomly assigned to atorvastatin 10 mg daily and a significant reduction in non-fatal MI, fatal CHD and stoke (fatal and non-fatal) was noticed. No significant difference was observed on all-cause mortality[9].
  • HPS (2003): In the sub-group of patients with diabetes without known occlusive vascular disease, Simvastatin 40 mg daily significantly reduced the rate of first major vascular events[10].

Risk factors

References

  1. ↑ Gordon DJ.Cholesterol lowering reduces mortality:the statins. In: Grundy SM, ed. Cholesterol-lowering therapy: evaluation of clinical trial evidence. New York:Marcel Dekker Inc., 2000:299-311
  2. ↑ Jenkins DJ, Jones PJ, Lamarche B, Kendall CW, Faulkner D, Cermakova L; et al. (2011). "Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial". JAMA. 306 (8): 831–9. doi:10.1001/jama.2011.1202. PMID 21862744.
  3. ↑ Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP; et al. (2011). "Statins for the primary prevention of cardiovascular disease". Cochrane Database Syst Rev (1): CD004816. doi:10.1002/14651858.CD004816.pub4. PMID 21249663.
  4. ↑ Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK (2006). "Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials". Arch Intern Med. 166 (21): 2307–13. doi:10.1001/archinte.166.21.2307. PMID 17130382. Review in: J Fam Pract. 2007 Mar;56(3):174
  5. ↑ Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW; et al. (1995). "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group". N Engl J Med. 333 (20): 1301–7. doi:10.1056/NEJM199511163332001. PMID 7566020.
  6. ↑ Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA; et al. (1998). "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study". JAMA. 279 (20): 1615–22. PMID 9613910.
  7. ↑ Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM; et al. (2002). "Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial". Lancet. 360 (9346): 1623–30. PMID 12457784. Review in: ACP J Club. 2003 Jul-Aug;139(1):9
  8. ↑ ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (2002). "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)". JAMA. 288 (23): 2998–3007. PMID 12479764. Review in: ACP J Club. 2003 Jul-Aug;139(1):10
  9. ↑ Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M; et al. (2003). "Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial". Lancet. 361 (9364): 1149–58. doi:10.1016/S0140-6736(03)12948-0. PMID 12686036. Review in: ACP J Club. 2003 Nov-Dec;139(3):57
  10. ↑ Collins R, Armitage J, Parish S, Sleigh P, Peto R, Heart Protection Study Collaborative Group (2003). "MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial". Lancet. 361 (9374): 2005–16. PMID 12814710. Review in: ACP J Club. 2004 Jan-Feb;140(1):1
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